The etiology of preeclampsia is unknown. Briefly, results from several studies (typically small studies not controlling for confounding) suggest that an imbalance in maternal antioxidant and pro-oxidant status may be associated with an increased risk of preeclampsia. There is also emerging evidence suggestive of an association between maternal proinflammatory status and increased risk of preeclampsia. In this competing renewal application, we seek to build on this body of work by continuing the prospective study (Epidemiology of Marine Fatty Acids and Preeclampsia: RO 1 HD 32562), and strategically integrating new biological markers that will serve to better characterize the epidemiology of preeclampsia. The study is a cohort study of 1,500 pregnant women enrolled early in pregnancy and followed until delivery. We plan to expand this cohort to include enrolling a total of 4,200 nulliparous women. We will use a nested case-cohort design and multivariate logistic analytical methods to assess the relation between risk of preeclampsia with biological markers of maternal antioxidant (enzymatic and non-enzymatic) status. Additionally, we will assess hypotheses concerning maternal chronic pro-inflammatory status [as measured by high sensitivity C-reactive protein (hs-CRP) and the pro-inflammatory cytokines including tumor necrosis factor-a (TNF-a)] soluble receptors (sTNFp55 and sTNFp75) in relation to preeclampsia risk. Our overall objective is to test whether dietary, immunological, and other lifestyle characteristics are associated with subsequent risk of developing preeclampsia. Results from our efforts should provide additional knowledge concerning the mechanistic basis for endothelial dysfunction and preeclampsia risk. Furthermore, our results should provide information that may be used to motivate the development of prevention intervention strategies sufficient for impacting the occurrence of preeclampsia. Results from the proposed study could have practical significance in developing alternative, practical preventative interventions for preeclampsia and other adverse pregnancy outcomes (e.g., fetal growth retardation and preterm delivery). Antioxidants, and trace metals such as zinc and selenium (which are important to the activity of antioxidant enzymes), as well as iron could be easily manipulated in the diet either by supplement use or by specific choice of foods if evidence from this and other studies indicates a benefit.